Auto-injector with needle shroud and needle protection cap

ABSTRACT

An auto-injector may be used to administer a dose of a liquid medicament (M). In some embodiments, a shroud is arranged inside a housing, the shroud slidable in longitudinal direction between at least a retracted position, in which a hollow injection needle is exposable and an advanced position, in which the needle is covered by the shroud. A protective needle shield is attachable to the needle in a manner to partially protrude beyond the proximal end of the shroud through the orifice with the needle in its advanced position. A syringe carrier is arranged inside the shroud and comprises at least one snap for locking it to the shroud in order to prevent relative axial motion. The snap is configured to automatically disengage upon removal of the protective needle shield to allow the syringe and needle to be retracted into the covered position under load of the syringe spring.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a U.S. National Phase Application pursuant to35 U.S.C. §371 of International Application No. PCT/EP2011/052304 filedFeb. 16, 2011, which claims priority to European Patent Application No.10154191.0 filed on Feb. 22, 2010. The entire disclosure contents ofthese applications are herewith incorporated by reference into thepresent application.

FIELD OF INVENTION

The invention relates to an auto-injector for administering a dose of aliquid medicament.

BACKGROUND

Administering an injection is a process which presents a number of risksand challenges for users and healthcare professionals, both mental andphysical.

Injection devices (i.e. devices capable of delivering medicaments from amedication container) typically fall into two categories—manual devicesand auto-injectors.

In a manual device—the user must provide the mechanical energy to drivethe fluid through the needle. This is typically done by some form ofbutton/plunger that has to be continuously pressed by the user duringthe injection. There are numerous disadvantages for the user from thisapproach. If the user stops pressing the button/plunger then theinjection will also stop. This means that the user can deliver anunderdose if the device is not used properly (i.e. the plunger is notfully pressed to its end position). Injection forces may be too high forthe user, in particular if the patient is elderly or has dexterityproblems.

The extension of the button/plunger may be too great. Thus it can beinconvenient for the user to reach a fully extended button. Thecombination of injection force and button extension can causetrembling/shaking of the hand which in turn increases discomfort as theinserted needle moves.

Auto-injector devices aim to make self-administration of injectedtherapies easier for patients. Current therapies delivered by means ofself-administered injections include drugs for diabetes (both insulinand newer GLP-1 class drugs), migraine, hormone therapies,anticoagulants etc.

Auto-injectors are devices which completely or partially replaceactivities involved in parenteral drug delivery from standard syringes.These activities may include removal of a protective syringe cap,insertion of a needle into a patient's skin, injection of themedicament, removal of the needle, shielding of the needle andpreventing reuse of the device. This overcomes many of the disadvantagesof manual devices. Forces required of the user/button extension,hand-shaking and the likelihood of delivering an incomplete dose arereduced. Triggering may be performed by numerous means, for example atrigger button or the action of the needle reaching its injection depth.In some devices the energy to deliver the fluid is provided by a spring.

Auto-injectors may be disposable or single use devices which may only beused to deliver one dose of medicament and which have to be disposed ofafter use. Other types of auto-injectors may be reusable. Usually theyare arranged to allow a user to load and unload a standard syringe. Thereusable auto-injector may be used to perform multiple parenteral drugdeliveries, where the syringe is disposed after having been spent andunloaded from the auto-injector. The syringe may be packaged withadditional parts to provide additional functionality.

US 2002/0095120 A1 discloses an automatic injection device whichautomatically injects a pre-measured quantity of fluid medicine when atension spring is released. The tension spring moves an ampoule and theinjection needle from a storage position to a deployed position when itis released. The content of the ampoule is thereafter expelled by thetension spring forcing a piston forward inside the ampoule. After thefluid medicine has been injected, energy stored in the tension spring isreleased and the injection needle is automatically retracted back to itsoriginal storage position.

Usually the hollow needle is equipped with a protective needle shieldfor keeping the needle sterile and preventing it from being mechanicallydamaged.

In order to prepare the auto-injector for delivering a dose theprotective needle shield has to be removed from the needle. This may bedone by gripping the protective needle shield and pulling it away fromthe needle. This will usually result in an exposed needle which isundesirable in terms of needle safety. In order to solve that problemthe needle and syringe could be arranged inside a needle shroud in amanner to hide the needle when the protective needle shield is removed.However, this would require the protective needle shield to be arrangedinside the needle shroud, too, making it virtually inaccessible for auser to be gripped.

SUMMARY

It is therefore an object of the present invention to provide anauto-injector with an improved needle protection.

The object is achieved by an auto-injector according to claim 1.

Preferred embodiments of the invention are given in the dependentclaims.

According to the invention, an auto-injector serves for administering adose of a liquid medicament. The auto-injector has a distal end and aproximal end with an orifice intended to be applied against an injectionsite. The auto-injector comprises:

an elongate housing arranged to contain a syringe with a hollow needleand a stopper for sealing the syringe and displacing the medicament,wherein the syringe is slidably arranged with respect to the housing,

a drive means capable of, upon activation:

-   -   pushing the needle from a covered position into an advanced        position through the orifice and past the proximal end, and    -   operating the syringe to supply the dose of medicament, and

activating means arranged to lock the drive means in a compressed stateprior to manual operation and capable of, upon manual operation,releasing the drive means for injection.

In the context of this specification the term “proximal” refers to thedirection pointing towards the patient during an injection while theterm “distal” refers to the opposite direction pointing away from thepatient. When referring to the proximal and distal portion of theauto-injector their respective distal and proximal ends are those thatpoint in the respective direction during an injection.

In the auto-injector according to the invention a shroud is arranged atleast partially inside the housing. The shroud is slidable inlongitudinal direction between at least a retracted position, in whichthe needle is exposable and an advanced position, in which the needle iscovered by the shroud. The shroud is arranged to be locked in theretracted position prior to manual operation of the activation means.Once the drive means has been released the shroud is unlocked andautomatically moves towards the advanced position under load of asyringe spring. This automatic movement will happen when theauto-injector is removed from the injection site in the course of aninjection or after the injection has been completed in order to hide theneedle and keep the user from injuring themselves. As long as the usermaintains the auto-injector pressed against the injection site duringthe injection cycle, the shroud will remain in the retracted position. Aprotective needle shield is attachable to the needle in a manner topartially protrude beyond the proximal end of the shroud through theorifice with the needle in its advanced position, which may be an “asshipped” state of the auto-injector. A syringe carrier is arrangedinside the shroud for holding the syringe. The syringe carrier isslidable with respect to the shroud. The syringe carrier comprises atleast one resilient snap for locking it to the shroud in order toprevent relative axial motion. The snap is arranged to be supportablefrom inside by the protective needle shield when attached to the needlein order to remain engaged with the shroud. The snap is inwardly biasedto disengage from the shroud without support from inside in a manner toautomatically disengage upon removal of the protective needle shield.Once the snap is disengaged, the syringe spring retracts the syringecarrier, the syringe and the needle into the covered position with theneedle hidden inside the shroud. In the state as shipped theauto-injector is needle safe due to the protective needle shield hidingthe needle. With the syringe and needle retracting immediately uponremoval of the protective needle shield the auto-injector remains needlesafe when armed.

The shroud may be slidable from the retracted position in the distaldirection into an unlocking position by a small distance against thebias of at least one flexural element which may be arranged at theshroud. Furthermore, interlocking means may be arranged to allow theactivating means to be operated only, when the shroud is in theunlocking position, wherein the interlocking means are arranged toprevent the activating means from being operated otherwise. Thus, a skininterlock feature is provided for making sure, the auto-injector isproperly positioned against the injection site before allowing theinjection to be triggered by the user.

At least one resilient latch may be arranged on the shroud for engagingin a respective recess of the housing when the shroud is translated intoits advanced position. Thus, post-injection needle safety is improvedsince the shroud cannot be pushed in distal direction again after theend of an injection cycle. In both cases, when the auto-injector isremoved from the injection site during injection or after delivering thefull dose the needle is covered and is needle safe.

In a preferred embodiment a gearbox is arranged for converting a firsttranslation into a second translation. The gearbox comprises a drivecollar connectable to the translative drive means, the drive collarprevented from rotating with respect to a ground of the drive means,which may be a housing or chassis or a grounding member fixed thereto. Adrive sleeve is rotatably arranged at least partially inside the drivecollar, engaged to the drive collar by a first screw thread andprevented from translating relative to the ground. A plunger is arrangedat least partially inside the drive sleeve, engaged to the drive sleeveby a second screw thread and prevented from rotating. The plunger is thecomponent for outputting the second translation. The gearbox is arrangedbetween the drive means and the syringe or the stopper in order to adaptthe force of the compression spring to the requirements of an injection.

The gearbox can modify, i.e. both reduce and amplify the distance andforce of the second translation relative to the first translation.

The drive means of the auto-injector is preferably arranged as acompression spring grounded at a distal end in a grounding member fixedto the housing, wherein a proximal end of the compression spring bearsagainst the drive collar.

When applied in an auto-injector with a compression spring as the drivemeans, the gearbox can be used to modify an amount of spring force thatis transmitted to a syringe or a stopper of the syringe.

Thus the spring force may be softened at the beginning of an injectioncycle when the spring force is highest in order to reduce impact loadsexperienced by components within the auto-injector. When applieddirectly to a glass syringe, the risk of breaking the glass by impact isremarkably reduced. Furthermore, user discomfort related to high impactloads is reduced. The dispense characteristics of the auto-injector maybe varied, e.g. in order to provide a rapid needle insertion, which isbelieved to offer benefits in terms of reducing the amount of pain feltby the patient. Furthermore, by adapting the transmitted force the dosemay be delivered more steadily and the repeatability of the timerequired for the injection cycle is improved. Otherwise, if the cycletimes are highly variable between different auto-injectors of the sametype, the user may be confused and make errors when delivering theinjection. The force available from the drive means may be modified forparticular operations of the device, e.g. steps in the operationalcycle, such as operating a latch mechanism to trigger needle retraction,may require a higher force, so the gearbox may be tailored to deliverthe required force. Particularly with a compression spring used as thedrive means the spring force decays with increasing extension of thespring. The gearbox may be adapted to compensate that decay. This may beused to eliminate the compromise between achieving a high end of doseload and minimizing the initial spring load. A dose delivery flow ratemay be kept constant.

The first screw thread and the second screw thread are like-handed, i.e.both right-handed or both left-handed.

In an alternative embodiment the drive sleeve may have an internal screwthread engaged with the plunger and the drive collar may have aninternal screw thread engaged with the drive sleeve.

The modification of the second translation (output) force and travelrelative to the first translation (input) is preferably achieved byvarying a pitch angle of the first screw thread and/or the second screwthread over the length of the respective screw thread.

The first screw thread and/or the second screw thread may comprise a camtrack in one of the engaged components and a ball or a follower in theother one of the engaged components. A ball held in a pocket in therespective component is preferred for its lower friction compared to afollower or peg. The screw threads may likewise have multiple parallelcam tracks, i.e. multi-start threads in order to distribute load to therespective number of followers or balls so the individual point load foreach follower or ball is reduced thereby improving the stability of themechanism and the smoothness of the transmission.

In one embodiment of the invention a number of teeth arecircumferentially arranged on an external surface of the drive sleeve. Asection of the shroud has internal splines for engaging with the teethin order to prevent rotation of the drive sleeve when the shroud is inits advanced position. Another section of the shroud proximally adjacentto the splined section is arranged to allow rotation of the drivesleeve. This feature allows for immediately stopping delivery of themedicament upon removal of the auto-injector from the injection siteprior to full dose delivery. This avoids continued displacement ofmedicament from the syringe after removing the auto-injector from theinjection site.

In an alternative embodiment of the invention, a transmissionarrangement for controlling a force of the drive means is providedinstead of the gearbox between the drive means and the syringe and/orthe stopper.

The transmission arrangement comprises a drive collar connectable to atranslative drive means and prevented from rotating with respect to aground of the drive means which may be the housing or a chassis or agrounding member fixed thereto. A flange face of the drive collar bearsagainst a mating flange face of a friction collar. The friction collaris slidable in longitudinal direction and rotationally constrained byengagement in a cam track. Another flange face of the friction collarbears against a mating flange face of a plunger. The plunger is slidablein longitudinal direction and prevented from rotating.

The plunger is the component for outputting the translation modified bythe transmission arrangement.

Rotation of the friction collar is defined by a pitch angle of the camtrack. The load on the friction collar is coupled to the rotationallyfixed, axially free plunger. The force of the drive means acting on bothmating surfaces of the friction collar towards the drive collar andtowards the plunger introduces a friction force opposing rotation. Asthe friction collar axially translates, it is forced to rotate by anysection of the cam track that is not parallel with a longitudinal axis.The friction collar will only rotate if the friction force between themating surfaces of the drive collar and the plunger is overcome. Thetorque to overcome this friction force is generated by the contact forcebetween the cam follower and the cam track, in which the cam follower isengaged. The contact force is generated by the spring force of the drivespring. A degree of coupling between the spring force and the contactforce is defined by the respective pitch angle of the cam track. By anappropriate modification to the cam track angle, the amount of springforce required to overcome the friction force can be modified. Forinstance, increasing the cam angle requires more of the spring force tobe reacted through the cam track, thereby reducing the force of thetranslation. The friction force is zero in straight sections of the camtrack in parallel with a longitudinal axis of the overall arrangement.With any non-zero pitch angle the friction force is introduced.

When applied in an auto-injector with a compression spring as the drivemeans, the transmission arrangement can be used to modify an amount ofspring force that is transmitted to a syringe or a stopper of thesyringe.

Thus the spring force may be softened at the beginning of an injectioncycle when the spring force is highest in order to reduce impact loadsexperienced by components within the auto-injector. When applieddirectly to a glass syringe, the risk of breaking the glass by impact isremarkably reduced. Furthermore, user discomfort related to high impactloads is reduced. The dispense characteristics of the auto-injector maybe varied, e.g. in order to provide a rapid needle insertion, which isbelieved to offer benefits in terms of reducing the amount of pain feltby the patient. Furthermore, by adapting the transmitted force the dosemay be delivered more steadily and the repeatability of the timerequired for the injection cycle is improved. Otherwise, if the cycletimes are highly variable between different auto-injectors of the sametype, the user may be confused and make errors when delivering theinjection. The force available from the drive means may be modified forparticular operations of the device, e.g. steps in the operationalcycle, such as operating a latch mechanism to trigger needle retraction,may require a higher force, so the transmission arrangement may betailored to deliver the required force. Particularly with a compressionspring used as the drive means the spring force decays with increasingextension of the spring. The transmission arrangement may be adapted tocompensate that decay by a pitch angle converging towards a straight,longitudinal section of the cam track, so at the end of the movement thefull force of the compression spring is available. Thus a dose deliveryflow rate may be kept constant.

The drive means may be a compression spring arranged over a shaft of agrounding member. The drive collar and the friction collar may bearranged in series with the compression spring and grounding member. Thecam track may be arranged in an external surface of the shaft the pinand a cam follower for engaging in the cam track may be arranged on thefriction collar.

Preferably the pitch angle of the cam track is varied over its length inorder to achieve the desired force of the translation.

There may be more than one cam track on the ground member shaft, thedifferent cam tracks with different pitch angle profiles, so the forcecontrol may be customized by selecting one of the cam tracks forengaging with the friction collar.

Instead of the planar flange faces the plunger, drive collar andfriction collar may have profiled or curved flange faces. In this case,rotation of the friction collar would introduce additional force controlby the varying angles of the mating faces. At the same time the distancetravelled by the plunger may be amplified or reduced by modifying anoverall length of the drive collar, friction collar and plunger when thefriction collar is rotated.

The friction collar and the shaft of the grounding member may bearranged to provide a ratchet feature to generate an audible userfeedback when the friction collar advances. Small raised features can bespaced in the cam track over which the follower has to pass. Thesefeatures can be profiled such that they induce vibration into the deviceas the dose is delivered.

In a preferred embodiment the plunger may comprise at least a hollowportion arranged for fitting onto the ground member shaft. Thus, theshaft serves for centring all components. The hollow portion may haveapertures in order to avoid the generation of a vacuum in the hollowportion when the plunger is being pushed off the shaft during thetranslation.

The hollow portion of the plunger may comprise an internal cam followerfor engaging in one of the straight, longitudinal sections of the camtrack, thus preventing rotation of the plunger.

In order to interlock the activation means or trigger button with theshroud at least one snap arm may be distally arranged at the drivecollar in a manner to be engageable behind a shoulder on the groundingmember in order to prevent expansion of the drive means. The snap armmay be disengageable from the shoulder by being pushed outward by arespective resilient extension of a trigger button. The resilientextension may be arranged to be flexed outward by pushing the triggerbutton in proximal direction thereby moving the resilient extensionalong a tapering surface of the grounding member which forces theresilient extension outwards. The shroud may be arranged to prevent atleast one of the resilient extensions from flexing outwards when theshroud is its retracted position. At least one distal recess may bearranged in the shroud for allowing a respective resilient extension tobe flexed outwards through the recess or aperture when the shroud is inan unlocking position.

The syringe spring may be arranged to bear against an internal shoulderin the shroud between a distal portion and a proximal portion andagainst a rear flange of the syringe carrier.

An intermediary component may be arranged for forwarding translation ofthe plunger to the syringe in order to first advance the syringe andneedle while avoiding load onto the stopper thus avoiding wet injection,i.e. medicament leaking out of the needle's tip before the needle isfully inserted into the injection site. The intermediary component isfurthermore arranged to be decoupled from the syringe when the needlehas reached a predefined injection depth. At the same time thetranslation is coupled to the stopper in order to inject the dose.

The term “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a proteine, apolysaccharide, a vaccine, a DNA, a RNA, a antibody, an enzyme, anantibody, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exedin-3 or exedin-4 or an analogue or derivative ofexedin-3 or exedin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N—(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

-   H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,-   H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,-   des Pro36 [Asp28] Exendin-4(1-39),-   des Pro36 [IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or-   des Pro36 [Asp28] Exendin-4(1-39),-   des Pro36 [IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),-   des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),-   wherein the group -Lys6-NH2 may be bound to the C-terminus of the    Exendin-4 derivative;-   or an Exendin-4 derivative of the sequence-   H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,-   des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,-   H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38[Asp28] Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,-   H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,-   des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,-   H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-Lys6-NH2,-   H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]    Exendin-4(1-39)-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]    Exendin-4(1-39)-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-NH2,-   des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2,-   H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(S1-39)-(Lys)6-NH2,-   H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]    Exendin-4(1-39)-(Lys)6-NH2;-   or a pharmaceutically acceptable salt or solvate of any one of the    afore-mentioned Exedin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

Further scope of applicability of the present invention will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating preferred embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will become more fully understood from thedetailed description given hereinbelow and the accompanying drawingswhich are given by way of illustration only, and thus, are not limitiveof the present invention, and wherein:

FIG. 1 is longitudinal sections in two section planes of anauto-injector with force control in an as shipped state,

FIG. 2 is the auto-injector during removal of a protective needleshield,

FIG. 3 is the auto-injector with a syringe carrier delatching from ashroud following the removal of the protective needle shield,

FIG. 4 is the auto-injector with the syringe carrier, syringe and aneedle being retracted into the shroud after delatching,

FIG. 5 is the auto-injector during deactivation of an interlock bypressing the shroud against an injection site,

FIG. 6 is the auto-injector during needle insertion into the injectionsite,

FIG. 7 is the auto-injector during removal from the injection site inthe course of an injection,

FIG. 8 is the auto-injector near the end of the injection,

FIG. 9 is the auto-injector withdrawn from the injection site afterhaving completed the injection, wherein the shroud extends to cover theneedle,

FIG. 10 is the auto-injector with the shroud locking into the housing,

FIG. 11 is a lateral view of a detail of an alternative embodiment of anauto-injector with force control with a friction collar,

FIG. 12 are three cross sections of the detail of FIG. 11, and

FIG. 13 is a longitudinal section of the detail of FIG. 11.

Corresponding parts are marked with the same reference symbols in allfigures.

DETAILED DESCRIPTION

FIG. 1 shows two longitudinal sections in two section planes of anauto-injector 1 with force control in an as shipped state. Theauto-injector 1 comprises an elongate housing 2, an essentially tubularshroud 3 arranged inside the housing 2 and slidable in longitudinaldirection with respect to the housing 2. A distal portion 3.1 of theshroud has an external diameter selected to fit into the housing 2. Thedistal portion 3.1 extends essentially through the entire housing 2 tothe distal end D. The biggest part of the distal portion 3.1 consists oftwo longitudinal extensions rather than a tube shape in order to allowother parts of the auto-injector 1 to engage in the housing 2 forpreventing relative rotation. This could alternatively be achieved by atubular distal portion 3.1 with longitudinal slots. A proximal portion3.2 of the shroud 3 has a reduced diameter compared to the distalportion 3.1 for slidably accommodating a syringe carrier 4. The syringecarrier 4 holds a syringe 5 and supports it at its proximal end in orderto avoid stress to its finger flanges 5.1. A hollow injection needle 6is attached to the proximal end of the syringe 5. A stopper 7 serves forsealing the distal end of the syringe 5. A liquid medicament M stored inthe syringe 5 may be displaced through the needle 6 by pushing thestopper 7 in proximal direction P by means of a plunger 8. In the asshipped state the syringe 5 and syringe carrier 4 are locked in positionthus providing a clearance between the plunger 8 and the stopper 7.Although the needle 6 protrudes beyond the proximal end P of theauto-injector 1, needle stick injuries are avoided by a protectiveneedle shield 9 attached to the needle 6 in the as shipped state. Thesyringe carrier 4 is biased in distal direction D with respect to theshroud 3 by means of a syringe spring 10 bearing against a shoulder 3.3in the shroud 3 and against a rear flange 4.1 in the syringe carrier 4.The shoulder 3.3 is defined between the distal portion 3.1 and theproximal portion 3.2. The rear flange 4.1 is arranged at the distal endof the syringe carrier 4. A drive spring 11 is arranged near the distalend D of the auto-injector 1 inside the shroud 3. The drive spring 11 ispreferably arranged as a compression spring. The distal end of the drivespring 11 is grounded in the housing 2 or in a grounding member 12 fixedto the housing 2. The proximal end of the drive spring 11 bears againsta drive collar 13 which is arranged inside the drive spring 11,rotationally fixed by splines 2.4 in the housing 2 but translatable inlongitudinal direction. Inside the drive collar 13 a drive sleeve 14 isarranged which in turn is arranged around the plunger 8. The drivesleeve 14 is rotationally free and axially fixed by distally bearingagainst the grounding member 12 and proximally bearing against a secondbulkhead 2.2. The plunger 8 is rotationally fixed and axially free. Thedrive collar 13 is engaged with the drive sleeve 14 by a first screwthread 15. The drive sleeve 14 is engaged with the plunger 8 by a secondscrew thread 16. Hence, when the drive collar 13 is pushed in proximaldirection P by the drive spring 11, the drive sleeve 14 is caused torotate which causes axial movement of the plunger 8. The first screwthread 15 and the second screw thread 16 are like-handed. By varying thepitch of the two screw threads 15, 16 a ratio of translation of thedrive collar 13 and the plunger 8 is changed and hence the transmittedforce is amplified or reduced.

The screw threads 15, 16 may have cam tracks and followers or ballbearings.

A syringe viewing window 17 for inspecting the syringe contents isprovided in the proximal portion 3.2 of the shroud 3.

A housing cap 18 and a trigger button 19 are arranged at the distal endD of the auto-injector 1.

In the shipped state in FIG. 1, the drive spring's 11 preload on thedrive collar 13 is statically resolved through distal snap arms 13.1 ofthe drive collar 13 which are engaged behind a shoulder 12.1 in thegrounding member 12. The syringe carrier 4 is prevented from moving inproximal direction P by the rear flange 4.1 bearing against a firstbulkhead 2.1 provided in the housing 2. Withdrawal of the shroud 3 intothe housing 2 is resisted by flexural elements 3.4 on the shroud 3acting against the first bulkhead 2.1 of the housing 2 from the proximalside (see FIG. 1 c for details). Extension of the shroud 3 in proximaldirection P is prevented by inward protrusions 3.5 contacting the drivecollar 13. The syringe carrier 4 is locked to the shroud 3 by at leasttwo snaps 4.2.

The protective needle shield 9 is interlocked to the syringe carrier 4.For this purpose the syringe carrier 4 has a pair of resilient snaps 4.2extending proximally beyond the section of the syringe carrier 4supporting the proximal end of the syringe 5. In the state as shippedthese snaps 4.2 are snapped into corresponding recesses provided in theproximal portion 3.2 of the shroud 3 thus preventing relative axialtranslation between the shroud 3 and the syringe carrier 4. The snaps4.2 are kept from flexing inwards and disengaging from the recesses bythe protective needle shield 9. The protective needle shield 9 protrudesbeyond the proximal end of the shroud 3 through an orifice.

In order to arm the auto-injector 1 the protruding part of theprotective needle shield 9 is gripped by a user and pulled off thesyringe 5 and needle 6 in proximal direction P (see FIG. 2). Once theprotective needle shield 9 has been removed the snaps 4.2 are no longersupported inwardly and disengage from the recesses 3.6 (see FIG. 3).Preferably the snaps 4.2 are biased to relax inwards when not supported.In an alternative embodiment the snaps 4.2 and the shroud 3 may haveangled mating surfaces for moving the snaps 4.2 inward thus disengagingthem from the recesses 3.6 under the force from the syringe spring 10when the snaps 4.2 are not supported inwardly. In this case the snaps4.2 do not have to be biased inwardly.

Now delatched from the shroud 3 the syringe carrier 4 together with thesyringe 5 and the needle 6 are translated in distal direction D due tothe load of the syringe spring 10 (see FIG. 4). Thus the needle 6 ishidden inside the shroud 3 and the user protected from accidental needlestick injuries.

In the next operating step the user places the proximal end P of theauto-injector 1 against an injection site, e.g. a patient's skin. Whencontacting the injection site the shroud 3 is depressed and translatesby a small distance in distal direction D into the housing 2 (see FIG.5) against the load of the flexural elements 3.4. As the shroud 3translates apertures in the shroud 3 move from a blocking positionagainst trigger button resilient extensions 19.1, thus unlocking thetrigger button 19.

The trigger button 19 comprises a number of resilient extensions 19.1facing the grounding member 12. The grounding member 12 has a taperingsurface 12.2 facing the trigger button 19. The resilient extensions 19.1are at least partially arranged inside the snap arms 13.1 of the drivecollar 13. When the trigger button 19 is pushed in proximal direction Pthe resilient extensions 19.1 contact the tapering surface 12.2 and aresplayed apart. Consequently, the resilient snap arms 13.1 are alsosplayed apart and disengaged from the shoulder 12.1 of the groundingmember 12. Thus, the drive collar 13 is no longer axially restricted andwill be released in the proximal direction P by the drive spring 11.

Before the shroud 3 is depressed (FIGS. 1 to 4) the distal portion 3.1of the shroud 3 prevents the trigger button's 19 resilient extensions19.1 from splaying out. As the shroud 3 is depressed (FIG. 5) it travelsin distal direction D to such an extend that the resilient extensions19.1 meet respective distal recesses 3.7 thus allowing the resilientextensions 19.1 to be splayed apart (see FIG. 5 c for details). At thesame time the syringe spring 10 is partially compressed by depressingthe shroud 3.

When the trigger button 19 is pressed and the drive collar 13 isdelatched from the grounding member 12 the force of the drive spring 11translates the drive collar 13 in proximal direction P (see FIG. 6).Rotation of the drive collar 13 is prevented by splined engagement inthe housing 2. The drive sleeve 14 is forced to rotate by engagement tothe drive collar 13 through the first screw thread 15. The plunger 8extends towards the stopper 7 by engagement to the drive sleeve 14through the second screw thread 16. The first screw thread 15 maycomprise an external, right-handed screw thread in the drive sleeve 14engaged with a ball located in a pocket on the internal surface of thedrive collar 13. The second screw thread 16 may comprise an externalright-handed screw thread in the plunger 8 engaged with a ball locatedin a pocket on the internal surface of the drive sleeve 14.Alternatively, both screw threads 15, 16 may be left-handed. Rotation ofthe plunger 8 is prevented by splined engagement in the grounding member12. This may be achieved by corresponding non-circular cross sections,e.g. square cross sections.

The gear ratio of the gear box comprising the drive collar 13, the firstscrew thread 15, the drive sleeve 14 and the second screw thread 16 isdefined by the pitch angles of the two screw threads 15, 16. If thepitch angle of the drive sleeve 14 is greater than that of the plunger8, the gear ration will be greater than 1, i.e. the gear box acts as adistance multiplier. Conversely, when the plunger 8 pitch angle isgreater than that of the drive sleeve 14, the gear ratio will be lessthan 1, i.e. the gear box acts as a force multiplier.

In an alternative embodiment the drive sleeve 14 may have an internalscrew thread engaged with the plunger 8 and the drive collar 13 may havean internal screw thread engaged with the drive sleeve 14.

As the plunger 8 travels forward it meets the stopper 7 and applies aforce on it which is resolved through the syringe spring 10. Thecounteracting force of the syringe spring 10 during compression has tobe greater than a counteracting force of the stopper 7 due to frictionbetween the stopper 7 and the inner wall of the syringe 5 and due to thehydrostatic resistance of the liquid medicament M to be displacedthrough the hollow needle 6. As the syringe spring 10 is compressed thesyringe carrier 4 travels in proximal direction P together with thesyringe 5 and the needle 6. Hence, the needle 6 is inserted into theinjection site. The injection depth is set by the rear flange 4.1 of thesyringe carrier 4 contacting the first bulkhead 2.1.

When the rear flange 4.1 hits the first bulkhead 2.1 the force of theplunger 8 pushes the stopper 7 in proximal direction P thus displacingthe liquid medicament M from the syringe 5 through the needle 6 and intothe injection site. During injection of the medicament M, the pitchangles of the screw threads 15, 16 may vary in order to adapt themechanical advantage of the gearbox.

FIGS. 7 a and 7 c show the auto-injector 1 during removal from theinjection site in the course of an injection cycle. If this happens, theshroud 3 will extend to cover the needle 6 under load of the syringespring 10. In parallel, internal splines 3.8 on the distal part 3.1 ofthe shroud 3 engage in teeth 14.1 on the outer surface of the drivesleeve 14. This prevents further rotation of the drive sleeve 14 andhence expansion of the plunger 8 and further emptying of the syringe 5.FIG. 7 b shows the drive sleeve 14 and the shroud 3 during injectionwith the shroud 3 persistently pressed against the injection site.Hence, the splines 3.8 and teeth 14.1 do not engage and the drive sleeve14 continues rotating. By contrast, FIG. 7 c shows the drive sleeve 14and the shroud 3 during removal of the auto-injector 1 from theinjection site in the course of an injection cycle. The shroud 3 istranslated in proximal direction P to an extent bringing the teeth 14.1and the splines 3.8 into engagement.

Even though the forward extension of the shroud 3 is limited by theposition of the drive collar 13, the auto-injector 1 is configured toprovide needle safety at all stages of the operational cycle:

With a transmission ratio of 1 or less as illustrated, as the needle isinserted into the injection site, the drive collar 13 moves in sync withthe syringe 5. Therefore, given that the needle 6 is initially fullycovered when the shroud 3 is fully extended and the needle 6 moves insync with the drive collar 13, the needle can not protrude a greaterdistance from the shroud 3 than the distance permitted by the drivecollar 13 and the inward protrusions 3.5. If the transmission ratio weregreater than 1, the design may be modified to position the needle 6further from the proximal end of the shroud 3 to ensure needle safety atall stages of the injection.

In FIG. 8 the stopper 7 has reached the end of the syringe 5 and thedose is fully delivered. The auto-injector 1 is sized so that thisoccurs prior to the drive collar 13 and/or plunger 8 reachingend-of-travel on their respective screw threads 15, 16, in particularbefore a flange 13.2 of the drive collar 13 contacts a flange 14.2 ofthe drive sleeve 14. The end of dose may be indicated to the user by anelapsed time (e.g. ten seconds), visible inspection through the syringeviewing window 17, or audible detection of movement of a ratchet engagedbetween any two parts with relative motion, for example the housing 2and the drive sleeve 14.

When the dose has been fully delivered the user may remove theauto-injector 1 from the injection site thus extracting the needle 6. Asthe auto-injector 1 is removed, the shroud 3 extends under bias of thesyringe spring 10 (see FIG. 9).

When the shroud 3 is at least almost fully extended, resilient latches3.9 in the distal portion 3.1 of the shroud 3 snap into respectiverecesses 2.3 arranged in the housing 2 thus preventing the shroud 3 frombeing pushed in distal direction D again, so post injection needlesafety is provided (FIG. 10). This applies for both cases, when theauto-injector 1 is removed from the injection site during injection(FIG. 7 a) or after delivering the full dose (FIG. 8).

The syringe carrier 4 has lateral apertures corresponding to the syringeviewing window 17 in order to allow visual inspection of the syringe 5.

In another embodiment the gearbox as shown in the preceding figurescomprising the drive collar 13, the first screw thread 15, the drivesleeve 14 and the second screw thread 16 may be replaced by a rotaryfriction element shown in FIGS. 11 to 13. The rotary friction elementcomprises a friction collar 20. In this embodiment the drive spring 11bears against the drive collar 13 which in turn pushes against thefriction collar 20 in sync with the plunger 8. At predetermined timesthe friction collar 20 is forced to rotate by its engagement in a camtrack 12.3 provided in the grounding member 12. For this purpose thefriction collar 20 has a cam follower 20.1.

As in the gearbox (FIG. 1) the drive collar 13 is rotationally fixed andaxially free. The friction collar 20 in contrast is axially free androtationally constrained by friction and by the cam track 12.3. Theplunger 8 comprises a hollow distal portion 8.1 fitting onto a shaft ofthe grounding member 12 and a proximal portion 8.2 with a reduceddiameter. The cross sections of both the hollow distal portion 8.1 andthe shaft of the grounding member 12 may be designed to prevent rotationof the plunger 8. For instance the plunger 8 may have a cam followerrunning in a straight section of the cam track 12.3. Rotation of thefriction collar 20 is defined by the cam track 12.3. The load on thefriction collar 20 is coupled to the rotationally fixed, axially freeplunger 8 which applies a force to the stopper 7. The compressive forceof the drive spring 11 acting on both mating surfaces of the frictioncollar 20 towards the drive collar 13 and towards the plunger 8introduces a friction force opposing rotation. As the friction collar 20axially translates, it is forced to rotate by any section of the camtrack 12.3 that is not parallel with the longitudinal axis of theauto-injector 1. The friction collar 20 will only rotate if the frictionforce between the mating surfaces of the drive collar 13 and the plunger8 is overcome. The torque to overcome this friction force is generatedby the contact force between the cam follower 20.1 and the cam track12.3, in which the cam follower 20.1 is engaged. The contact force isgenerated by the spring force of the drive spring 11. A degree ofcoupling between the spring force and the contact force is defined bythe respective angle of the cam track 12.3. By an appropriatemodification to the cam track angle, the amount of spring force requiredto overcome the friction force can be modified. For instance, increasingthe cam angle requires more of the spring force to be reacted throughthe cam track 12.3, thereby reducing the force applied to the stopper 7.

In an alternative embodiment an intermediary component may be providedfor first coupling the plunger 8 to the syringe carrier 4 or the syringe5 directly without acting on the stopper 7 until the needle 6 hasreached its injection depth. The plunger 8 would then be decoupled fromthe syringe 5 or syringe carrier 4 by the intermediary component andinstead be coupled to the stopper 7 in order to displace the medicamentM from the syringe 5. Thus, wet injection is avoided, i.e. themedicament is not leaking out of the needle tip before the needle isinserted. The intermediary component may be a transfer sleeve or anadditional feature at the syringe carrier 4. The transfer sleeve andplunger 8 would be initially coupled and translate together. However,when the syringe carrier 4 nears the end of its travel during needleinsertion, the transfer sleeve would decouple from the plunger. Fromthis point forwards, the plunger 8 load would be transferred directly tothe stopper 7. This decoupling arrangement may be embodied in anysuitable auto-injector arrangement. For example, the transfer sleevecould be clipped to the plunger by some clips. Near the end of travelthe clips could find some place to splay or be pushed away from theplunger 8 in order to decouple the plunger 8 from the transfer sleeve.

The invention claimed is:
 1. An auto-injector for administering a doseof a liquid medicament (M), the auto-injector having a distal end (D)and a proximal end P with an orifice intended to be applied against aninjection site and comprising: an elongate housing arranged to contain asyringe with a hollow needle and a stopper for sealing the syringe anddisplacing the medicament (M), wherein the syringe is slidably arrangedwith respect to the housing, a driver capable of, upon activation:pushing the needle from a covered position into an advanced positionthrough the orifice and past the proximal end (P), and operating thesyringe to supply the dose of medicament (M), and a trigger mechanismarranged to lock the driver in a compressed state prior to manualoperation and capable of, upon manual operation, releasing the driverfor injection, characterized in that a shroud is arranged at leastpartially inside the housing, the shroud slidable in longitudinaldirection between at least a retracted position, in which the needle isexposable and an advanced position, in which the needle is covered bythe shroud, wherein the shroud is arranged to be locked in the retractedposition prior to manual operation of the trigger mechanism and whereinthe shroud is arranged to be pushed towards the advanced position by asyringe spring when the driver has been released, wherein a protectiveneedle shield is attachable to the needle in a manner to partiallyprotrude beyond the proximal end of the shroud through the orifice withthe needle in its advanced position, wherein a syringe carrier isarranged inside the shroud for holding the syringe, the syringe carrierslidable with respect to the shroud, wherein the syringe carriercomprises at least one resilient snap for locking it to the shroud inorder to prevent relative axial motion, wherein the snap is arranged tobe supportable from inside by the protective needle shield when attachedto the needle in order to remain engaged with the shroud and wherein thesnap is inwardly biased to disengage from the shroud without supportfrom inside in a manner to automatically disengage upon removal of theprotective needle shield, thus allowing the syringe and needle to beretracted into the covered position under load of the syringe spring. 2.The auto-injector according to claim 1, characterized in that the shroudis slidable from the retractable position in distal direction (D) intoan unlocking position by a small distance against the bias of at leastone flexural element, wherein a plurality of protrusions are arranged toallow the trigger mechanism to be operated only, when the shroud is inthe unlocking position, wherein the plurality of protrusions arearranged to prevent the trigger mechanism from being operated otherwise.3. The auto-injector according to claim 1, characterized in that atleast one resilient latch arranged at the shroud for engaging in arespective recess of the housing when the shroud is translated into itsadvanced position.
 4. The auto-injector according to claim 1,characterized in that a gearbox for converting a first translation ofthe driver into a second translation of a plunger is arranged betweenthe driver and the syringe or the stopper, the gearbox comprising adrive collar connectable to the driver and prevented from rotating withrespect to a ground of the driver, a drive sleeve rotatably arranged atleast partially inside the drive collar, engaged to the drive collar bya first screw thread and prevented from translating, wherein the plungeris arranged at least partially inside the drive sleeve, engaged to thedrive sleeve by a second screw thread and prevented from rotating. 5.The auto-injector according claim 4, characterized in that a pitch angleof the first screw thread and/or the second screw thread vary/variesover the length of the respective screw thread.
 6. The auto-injectoraccording to claim 4, characterized in that the first screw threadand/or the second screw thread comprise a cam track in one of theengaged components and a ball or a follower in the other one of theengaged components.
 7. The auto-injector according to claim 1,characterized in that teeth are circumferentially arranged on anexternal surface of the drive sleeve, wherein a section of the shroudhas internal splines for engaging with the teeth in order to preventrotation of the drive sleeve when the shroud is in its advancedposition, wherein another section of the shroud proximally adjacent tothe splined section is arranged to allow rotation of the drive sleeve.8. The auto-injector according to claim 1, characterized in that atransmission arrangement for controlling a force of the translation ofthe driver is arranged between the driver and the syringe or thestopper, the transmission arrangement comprising a drive collarconnectable to the translative driver and prevented from rotating withrespect to a ground of the driver, a flange face of the drive collarbearing against a mating flange face of a friction collar, the frictioncollar slidable in longitudinal direction and rotationally constrainedby engagement in a cam track, another flange face of the friction collarbearing against a mating flange face of a plunger, the plunger slidablein longitudinal direction and prevented from rotating.
 9. Theauto-injector according to claim 8, characterized in that the driver isa compression spring arranged on a pin of a grounding member, whereinthe drive collar and the friction collar are arranged in series with thecompression spring on the pin, wherein the cam track is arranged in thepin and wherein a cam follower for engaging in the cam track is arrangedat the friction collar.
 10. The auto-injector according to claim 8,characterized in that a pitch angle of the cam track is varied over itslength.
 11. The auto-injector according to claim 8, characterized inthat the cam track comprises at least one straight, longitudinalsection.
 12. The auto-injector arrangement according to claim 8,characterized in that the plunger comprises at least a hollow portionarranged for fitting onto the pin.
 13. The auto-injector according toclaim 12, characterized in that the plunger comprises a cam follower forengaging in one of the straight, longitudinal sections of the cam track.14. The auto-injector according to claim 4, characterized in that atleast one snap arm is distally arranged at the drive collar in a mannerto be engageable behind a shoulder on the grounding member in order toprevent expansion of the driver, the snap arm disengageable from theshoulder by being pushed outward by a respective resilient extension ofa trigger button, the resilient extension arranged to be flexed outwardby pushing the trigger button in proximal direction (P), thereby movingthe resilient extension along a tapering surface of the groundingmember, wherein the shroud is arranged to prevent at least one of theresilient extensions from flexing outwards when in the retractedposition and wherein at least one distal recess is arranged in theshroud for allowing a respective resilient extension to be flexedoutwards when the shroud is in its unlocking position.